Texaphyrins, pentaaza Schiff base macrocycles, share a strong, but ‘expanded’, similarity to porphyrins and derivatives. Discovered decades ago,[1] texaphyrins have exhibited a variety of attractive intrinsic properties. With demonstrated capabilities of forming stable 1:1 complexes with a wide range of metal cations (particularly trivalent lanthanides), applications of texaphyrins were observed in cancer therapy and imaging.[2] Absorbing strongly in the tissue-transparent 700-900 nm range, texaphyrins offer a unique capability of in vivo excitation through external photon sources. In addition to these properties, texaphyrins exhibit inherent selective biolocalization in certain tissues, as well as having selectivity to tumours.
Efforts have been made to enhance the efficacy and selectivity of texaphyrins through conjugation methodologies. One such example is the use of texaphyrin as a “carrier” to overcome platinum drug resistance in cancer therapy,[3] involving the conjugation of texaphyrin to platinum drugs (i.e. cisplatin), through covalent linkage at the benzylic position. Moreover, lipophilic molecules have been conjugated with texaphyrins in an effort to incorporate into a biological vesicle.[4]
Conjugation of biologically active compounds to texaphyrins serve several benefits: i) the intrinsic tumour selectivity of texaphyrins can reduce aspecific toxicity of certain drugs; ii) addition of hydrophilic units can aid in the water solubility of texaphyrins, thereby increasing bioavailability; and iii) conjugation of texaphyrin to a targeting moiety can increase localization and accumulation in target tissues. Exploring novel texaphyrin conjugates offers an avenue into building upon demonstrated therapeutically relevant properties of texaphyrins, in applications pertaining to cancer therapy and imaging.